The first objective of this investigation is to preserve platelet numbers and function during extracorporeal perfusion so that platelets can function normally immediately after bypass stops, and that bleeding times and wound hemostasis will be normal. To achieve this objective we will study platelets within an in vitro extra-corporeal test circuit containing a membrane or bubble oxygenator or within a simulated cardiotomy sucker circuit. We will intensively characterize platelet behaviour during extracorporeal perfusion using a selected group of platelet function studies, biochemical studies of released substances (acid hydrolases, malondialdehyde, lactoferrin), and studies of platelet membranes. We will study selected platelet inhibitors, prostaglandin E1, prostacyclin (PGI2), and derivatives and analogs of PGI2. We will also study platelet inhibitors that are chemically bound to silicone rubber circuits. Toxicity studies, in vivo total bypass experiments, and clinical trials of the most successful reversible platelet inhibitors that achieve the objectives will be carried out. We will test the hypothesis that surfaces initiate coagulation only through direct activation of platelets and Factor XII (Hageman factor). We will test for Hageman factor activation by measurement of pre-kallikrein and kallikrein-inhibitor complex in our test circuits and will attempt to show that other coagulation factors are not activated by surfaces during extracorporeal perfusion in studies of Factor VIII deficient blood. We will inhibit Hageman factor activation by selected inhibitors (cytochrome c, spermine tetrachloride, lysozyme) and attempt to recirculate fresh, human blood without heparin using platelet and Factor XII inhibitors only. Successful prevention of thrombosis and emboli by the use of selected inhibitors to surface activation (i.e. platelets and Factor XII) should obviate the need for heparin, which globally inhibits multiple coagulation factors, and causes wound bleeding, leave intact the intrinsic and common coagulation pathways and permit normal wound hemostasis and bleeding times during partial long-term cardiopulmonary bypass.